Drugs

Reviewers Question Sarepta DMD Drug

David McFarland

— 1 min read
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The FDA Cellular, Tissue, and Gene Therapies Advisory Committee meets 5/12 to consider a Sarepta BLA seeking accelerated approval for its SRP-9001 (delandistrogene moxeparvovec), an adeno-associated virus vector-based gene therapy product, to treat ambulatory patients with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. A briefing document issued in advance of the meeting says agency medical reviewers found that “the clinical studies conducted to data do not provide unambiguous evidence that SRP-9001 is likely beneficial for ambulatory patients with DMD.”

The document says it is challenging to conclude with reasonable certainty from the data provided by Sarpeta either that SRP-9001 is likely effective for younger patients or that it is likely ineffective for older patients or those with somewhat poorer functional status. It also says FDA reviewers have concerns about the safety of possibly administering an ineffective gene therapy.

Committee members are asked to consider:

  • whether expression of Sarepta’s micro-dystrophin protein at week 12 after administration of SRP-9001 can serve as a surrogate endpoint that is reasonably likely to predict clinical benefit in support of a BLA for accelerated approval;
  • the potential clinical implications of findings, including exploratory subgroup analyses, from the only randomized clinical study;
  • the potential benefits, risks, and uncertainties that may be associated with the administration of SRP-9001 to treat ambulatory patients with DMD in the context of accelerated approval; and
  • the potential impact of granting accelerated approval on the ability to bring to a conclusion the ongoing randomized 52-week Part 1 of study SRP-9001-301, which is proposed to serve as the required postmarketing confirmatory trial to verify and describe clinical benefit, without missing the collection of critical data.

The committee ultimately will be asked to vote on whether the overall considerations of benefits and risk, taking into account the existing uncertainties, support accelerated approval of SRP-9001, using as a surrogate endpoint the expression of Sarepta’s micro-dystrophin at week 12 after administration, for the treatment of ambulatory patients with DMD with a confirmed mutation in the DMD gene.

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